|
Binding affinity of a compound to rat brain 5-hydroxytryptamine 1A (serotonin) receptor assayed by radiolabeled [3H]-8-OH-DPAT ligand displacement
|
None
|
3.162
nM
|
|
Journal : J. Med. Chem.
Title : Binding of arylpiperazines, (aryloxy)propanolamines, and tetrahydropyridylindoles to the 5-HT1A receptor: contribution of the molecular lipophilicity potential to three-dimensional quantitative structure-affinity relationship models.
Year : 1996
Volume : 39
Issue : 1
First Page : 126
Last Page : 134
Authors : Gaillard P, Carrupt PA, Testa B, Schambel P.
Abstract : A set of 280 5-HT1A receptor ligands were selected from available literature data according to predefined criteria and subjected to three-dimensional quantitative structure-affinity relationship analysis using comparative molecular field analysis. No model was obtained for serotonin analogues (19 compounds) and aminotetralins (60 compounds), despite a variety of alignment hypotheses being tried. In contrast, the steric, electrostatic, and lipophilicity fields alone and in combination yielded informative models for arylpiperazines (101 training compounds and 12 test compounds), (aryloxy)propanolamines (30 training compounds and four test compounds), and tetrahydropyridylindoles (54 training compounds) taken separately (models A, B, and C). Arylpiperazines and (aryloxy)propanolamines were then combined successfully to yield reasonably good models for 131 compounds (model D). In a last step, the three chemical classes (185 compounds) were combined, again successfully (model E). This stepwise procedure not only ascertains self-consistency in alignments but it also allows statistical signals (i.e., favorable or unfavorable regions around molecules) to emerge which cannot exist in a single chemical class. The models so obtained reveal a number of interaction sites between ligands and the 5-HT1A receptor, and extend the information gathered from a model based on homology modeling.
|
Inhibition of veratridine-induced guanidine flux in cardiac voltage-gated sodium channel (veratridine block vs. Na release)
|
Rattus norvegicus
|
306.0
nM
|
|
Journal : J. Med. Chem.
Title : Medicinal chemistry of neuronal voltage-gated sodium channel blockers.
Year : 2001
Volume : 44
Issue : 2
First Page : 115
Last Page : 137
Authors : Anger T, Madge DJ, Mulla M, Riddall D.
|
Inhibitory concentration against IKr potassium channel
|
None
|
350.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : The pharmacophore hypotheses of I(Kr) potassium channel blockers: novel class III antiarrhythmic agents.
Year : 2004
Volume : 14
Issue : 18
First Page : 4771
Last Page : 4777
Authors : Du LP, Tsai KC, Li MY, You QD, Xia L.
Abstract : Predictive pharmacophore models were developed for a large series of I(Kr) potassium channel blockers as class III antiarrhythmic agents using HypoGen in Catalyst software. The pharmacophore hypotheses were generated using a training set consisting of 34 compounds carefully selected from documents. Their biological data, expressed as IC(50), spanned from 1.5 nM to 2.8 mM with 7 orders difference. The most predictive hypothesis (Hypo1), consisting of four features (one positive ionizable feature, two aromatic rings and one hydrophobic group), had a best correlation coefficient of 0.825, a lowest rms deviation of 1.612, and a highest cost difference (null cost-total cost) of 77.552, which represents a true correlation and a good predictivity. The hypothesis Hypo1 was then validated by a test set consisting of 21 compounds and by a cross-validation of 95% confidence level with randomizing the data using CatScramble program. Accordingly, our model has strong predictivity to identify structural diverse I(Kr) potassium channel blockers with desired biological activity by virtual screening
|
Displacement of [3H]prazosin from alpha1 adrenergic receptor in rat cerebral cortex by liquid scintillation method
|
Rattus norvegicus
|
2.2
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and adrenolytic activity of 1-(1H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol and its enantiomers. Part 1.
Year : 2009
Volume : 44
Issue : 2
First Page : 809
Last Page : 817
Authors : Groszek G, Bednarski M, Dybała M, Filipek B.
Abstract : The synthesis of (2RS)-1-(1H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol ((RS)-9) and its enantiomers has been described and tested for electrocardiographic, antiarrhythmic, hypotensive and spasmolytic activities as well as for alpha(1)-, alpha(2)- and beta(1)-adrenoceptors' binding affinities. All compounds significantly decrease systolic and diastolic blood pressure, and possess antiarrhythmic activity and affinity to alpha(1)-, alpha(2)- and beta(1)-adrenoceptors. The results suggest that the antiarrhythmic and hypotensive effects of these compounds are related to their adrenolytic but not spasmolytic properties.
|
Displacement of [3H]clonidine from alpha2 adrenergic receptor in rat cerebral cortex by liquid scintillation method
|
Rattus norvegicus
|
3.4
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and adrenolytic activity of 1-(1H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol and its enantiomers. Part 1.
Year : 2009
Volume : 44
Issue : 2
First Page : 809
Last Page : 817
Authors : Groszek G, Bednarski M, Dybała M, Filipek B.
Abstract : The synthesis of (2RS)-1-(1H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol ((RS)-9) and its enantiomers has been described and tested for electrocardiographic, antiarrhythmic, hypotensive and spasmolytic activities as well as for alpha(1)-, alpha(2)- and beta(1)-adrenoceptors' binding affinities. All compounds significantly decrease systolic and diastolic blood pressure, and possess antiarrhythmic activity and affinity to alpha(1)-, alpha(2)- and beta(1)-adrenoceptors. The results suggest that the antiarrhythmic and hypotensive effects of these compounds are related to their adrenolytic but not spasmolytic properties.
|
Displacement of [3H]CGP12177 from beta-1 adrenergic receptor in rat cerebral cortex by liquid scintillation method
|
Rattus norvegicus
|
0.81
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and adrenolytic activity of 1-(1H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol and its enantiomers. Part 1.
Year : 2009
Volume : 44
Issue : 2
First Page : 809
Last Page : 817
Authors : Groszek G, Bednarski M, Dybała M, Filipek B.
Abstract : The synthesis of (2RS)-1-(1H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol ((RS)-9) and its enantiomers has been described and tested for electrocardiographic, antiarrhythmic, hypotensive and spasmolytic activities as well as for alpha(1)-, alpha(2)- and beta(1)-adrenoceptors' binding affinities. All compounds significantly decrease systolic and diastolic blood pressure, and possess antiarrhythmic activity and affinity to alpha(1)-, alpha(2)- and beta(1)-adrenoceptors. The results suggest that the antiarrhythmic and hypotensive effects of these compounds are related to their adrenolytic but not spasmolytic properties.
|
Displacement of [3H]Prazosin from alpha1 adrenergic receptor in Wistar rat cerebral cortex membrane by liquid scintillation counting
|
Rattus norvegicus
|
2.2
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and adrenolytic activity of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxy phenoxy)ethylamino)propan-2-ol analogs and its enantiomers. Part 2.
Year : 2009
Volume : 44
Issue : 12
First Page : 5103
Last Page : 5111
Authors : Groszek G, Nowak-Król A, Wdowik T, Swierczyński D, Bednarski M, Otto M, Walczak M, Filipek B.
Abstract : The synthesis of (2RS)-1-(5-methoxy-1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol and (2RS)-1-(7-methoxy-1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol and its enantiomers, analogs of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol ((RS)-9) is described. Compounds were tested for electrographic, antiarrhythmic, hypotensive and spasmolytic activities as well as for alpha(1)-, alpha(2)- and beta(1)-adrenoceptors binding affinities. The antagonist potency of the new compounds was compared with carvedilol and (RS)-9.
|
Displacement of [3H]Clonidine from alpha2 adrenergic receptor in Wistar rat cerebral cortex membrane by liquid scintillation counting
|
Rattus norvegicus
|
3.4
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and adrenolytic activity of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxy phenoxy)ethylamino)propan-2-ol analogs and its enantiomers. Part 2.
Year : 2009
Volume : 44
Issue : 12
First Page : 5103
Last Page : 5111
Authors : Groszek G, Nowak-Król A, Wdowik T, Swierczyński D, Bednarski M, Otto M, Walczak M, Filipek B.
Abstract : The synthesis of (2RS)-1-(5-methoxy-1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol and (2RS)-1-(7-methoxy-1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol and its enantiomers, analogs of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol ((RS)-9) is described. Compounds were tested for electrographic, antiarrhythmic, hypotensive and spasmolytic activities as well as for alpha(1)-, alpha(2)- and beta(1)-adrenoceptors binding affinities. The antagonist potency of the new compounds was compared with carvedilol and (RS)-9.
|
Displacement of [3H]CGP12177 from beta-1 adrenergic receptor in Wistar rat cerebral cortex membrane by liquid scintillation counting
|
Rattus norvegicus
|
0.81
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis and adrenolytic activity of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxy phenoxy)ethylamino)propan-2-ol analogs and its enantiomers. Part 2.
Year : 2009
Volume : 44
Issue : 12
First Page : 5103
Last Page : 5111
Authors : Groszek G, Nowak-Król A, Wdowik T, Swierczyński D, Bednarski M, Otto M, Walczak M, Filipek B.
Abstract : The synthesis of (2RS)-1-(5-methoxy-1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol and (2RS)-1-(7-methoxy-1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol and its enantiomers, analogs of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol ((RS)-9) is described. Compounds were tested for electrographic, antiarrhythmic, hypotensive and spasmolytic activities as well as for alpha(1)-, alpha(2)- and beta(1)-adrenoceptors binding affinities. The antagonist potency of the new compounds was compared with carvedilol and (RS)-9.
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT1A radioligand binding (ligand: [3H] 8-OH-DPAT)
|
None
|
5.842
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT1A radioligand binding (ligand: [3H] 8-OH-DPAT)
|
None
|
3.338
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT1B radioligand binding (ligand: [125I] Cyanopindolol)
|
Rattus norvegicus
|
589.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: [3H] Ketanserin)
|
None
|
410.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: [3H] Ketanserin)
|
None
|
117.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
7.789
nM
|
|
DRUGMATRIX: Alpha-1A adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
3.153
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
3.551
nM
|
|
DRUGMATRIX: Alpha-1B adrenergic receptor radioligand binding (ligand: prazosin)
|
Rattus norvegicus
|
1.966
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-1D adrenergic receptor radioligand binding (ligand: prazosin)
|
None
|
1.796
nM
|
|
DRUGMATRIX: Alpha-1D adrenergic receptor radioligand binding (ligand: prazosin)
|
None
|
0.883
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912)
|
None
|
106.0
nM
|
|
DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912)
|
None
|
40.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscine)
|
None
|
94.0
nM
|
|
DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscine)
|
None
|
43.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Adrenergic Alpha-2C radioligand binding (ligand: [3H] MK-912)
|
None
|
90.0
nM
|
|
DRUGMATRIX: Adrenergic Alpha-2C radioligand binding (ligand: [3H] MK-912)
|
None
|
13.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Adrenergic beta1 radioligand binding (ligand: [125I] Cyanopindolol)
|
None
|
0.178
nM
|
|
DRUGMATRIX: Adrenergic beta1 radioligand binding (ligand: [125I] Cyanopindolol)
|
None
|
0.103
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Adrenergic beta2 radioligand binding (ligand: [3H] CGP-12177)
|
None
|
0.241
nM
|
|
DRUGMATRIX: Adrenergic beta2 radioligand binding (ligand: [3H] CGP-12177)
|
None
|
0.166
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Adrenergic beta3 radioligand binding (ligand: [125I] Cyanopindolol)
|
None
|
4.155
nM
|
|
DRUGMATRIX: Adrenergic beta3 radioligand binding (ligand: [125I] Cyanopindolol)
|
None
|
3.116
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
538.0
nM
|
|
DRUGMATRIX: Norepinephrine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
533.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Calcium Channel Type L, Benzothiazepine radioligand binding (ligand: [3H] Diltiazem)
|
Rattus norvegicus
|
621.0
nM
|
|
DRUGMATRIX: Calcium Channel Type L, Benzothiazepine radioligand binding (ligand: [3H] Diltiazem)
|
Rattus norvegicus
|
552.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
23.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
15.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: [3H] Mesulergine)
|
None
|
115.0
nM
|
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2C radioligand binding (ligand: [3H] Mesulergine)
|
None
|
60.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT4 radioligand binding (ligand: [3H] GR-113808)
|
Cavia porcellus
|
181.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT6 radioligand binding (ligand: [3H] Lysergic acid diethylamide)
|
None
|
705.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand binding (ligand: [3H] Paroxetine)
|
None
|
221.0
nM
|
|
DRUGMATRIX: Transporter, Serotonin (5-Hydroxytryptamine) (SERT) radioligand binding (ligand: [3H] Paroxetine)
|
None
|
118.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Sodium Channel, Site 2 radioligand binding (ligand: [3H] Batrachotoxin)
|
Rattus norvegicus
|
455.0
nM
|
|
DRUGMATRIX: Sodium Channel, Site 2 radioligand binding (ligand: [3H] Batrachotoxin)
|
Rattus norvegicus
|
415.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Calcium Channel Type L, Phenylalkylamine radioligand binding (ligand: [3H] (-)-Desmethoxyverapamil (D-888))
|
Rattus norvegicus
|
389.0
nM
|
|
DRUGMATRIX: Calcium Channel Type L, Phenylalkylamine radioligand binding (ligand: [3H] (-)-Desmethoxyverapamil (D-888))
|
Rattus norvegicus
|
378.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Dopamine D1 radioligand binding (ligand: [3H] SCH-23390)
|
None
|
749.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Dopamine D2L radioligand binding (ligand: [3H] Spiperone)
|
None
|
146.0
nM
|
|
DRUGMATRIX: Dopamine D2L radioligand binding (ligand: [3H] Spiperone)
|
None
|
49.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone)
|
None
|
577.0
nM
|
|
DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone)
|
None
|
196.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
DRUGMATRIX: Dopamine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
845.0
nM
|
|
DRUGMATRIX: Dopamine Transporter radioligand binding (ligand: [125I] RTI-55)
|
None
|
671.0
nM
|
|
Title : DrugMatrix in vitro pharmacology data
Authors : Scott S. Auerbach, DrugMatrix¨ and ToxFX¨ Coordinator National Toxicology Program
Abstract : The DrugMatrix Pharmacology data is a subset of the data freely available from the National Toxicology Program. For more details see:https://ntp.niehs.nih.gov/drugmatrix/index.html
|
Inhibition of mouse Ido2 transfected in HEK293T cells using L-tryptophan as substrate assessed as kynurenine formation at 20 uM after 45 mins by spectrophotometric analysis relative to control
|
Mus musculus
|
55.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Identification of selective inhibitors of indoleamine 2,3-dioxygenase 2.
Year : 2012
Volume : 22
Issue : 24
First Page : 7641
Last Page : 7646
Authors : Bakmiwewa SM, Fatokun AA, Tran A, Payne RJ, Hunt NH, Ball HJ.
Abstract : The kynurenine pathway is responsible for the breakdown of the majority of the essential amino acid, tryptophan (Trp). The first and rate-limiting step of the kynurenine pathway can be independently catalysed by tryptophan 2,3-dioxygenase (Tdo2), indoleamine 2,3-dioxygenase 1 (Ido1) or indoleamine 2,3-dioxygenase 2 (Ido2). Tdo2 or Ido1 enzymatic activity has been implicated in a number of actions of the kynurenine pathway, including immune evasion by tumors. IDO2 is expressed in several human pancreatic cancer cell lines, suggesting it also may play a role in tumorigenesis. Although Ido2 was originally suggested to be a target of the chemotherapeutic agent dextro-1-methyl-tryptophan, subsequent studies suggest this compound does not inhibit Ido2 activity. The development of selective Ido2 inhibitors could provide valuable tools for investigating its activity in tumor development and normal physiology. In this study, a library of Food and Drug Administration-approved drugs was screened for inhibition of mouse Ido2 enzymatic activity. A number of candidates were identified and IC(50) values of each compound for Ido1 and Ido2 were estimated. The Ido2 inhibitors were also tested for inhibition of Tdo2 activity. Our results showed that compounds from a class of drugs used to inhibit proton pumps were the most potent and selective Ido2 inhibitors identified in the library screen. These included tenatoprazole, which exhibited an IC(50) value of 1.8μM for Ido2 with no inhibition of Ido1 or Tdo2 activity detected at a concentration of 100μM tenatoprazole. These highly-selective Ido2 inhibitors will be useful for defining the distinct biological roles of the three Trp-catabolizing enzymes.
|
Inhibition of human MATE1-mediated ASP+ uptake expressed in HEK293 cells at 20 uM after 1.5 mins by fluorescence assay
|
Homo sapiens
|
21.0
%
|
|
Journal : J. Med. Chem.
Title : Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling.
Year : 2013
Volume : 56
Issue : 3
First Page : 781
Last Page : 795
Authors : Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM.
Abstract : The human multidrug and toxin extrusion (MATE) transporter 1 contributes to the tissue distribution and excretion of many drugs. Inhibition of MATE1 may result in potential drug-drug interactions (DDIs) and alterations in drug exposure and accumulation in various tissues. The primary goals of this project were to identify MATE1 inhibitors with clinical importance or in vitro utility and to elucidate the physicochemical properties that differ between MATE1 and OCT2 inhibitors. Using a fluorescence assay of ASP(+) uptake in cells stably expressing MATE1, over 900 prescription drugs were screened and 84 potential MATE1 inhibitors were found. We identified several MATE1 selective inhibitors including four FDA-approved medications that may be clinically relevant MATE1 inhibitors and could cause a clinical DDI. In parallel, a QSAR model identified distinct molecular properties of MATE1 versus OCT2 inhibitors and was used to screen the DrugBank in silico library for new hits in a larger chemical space.
|
Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media, using NBS plates, by OD(600)
|
Staphylococcus aureus subsp. aureus
|
10.39
%
|
|
|
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600)
|
Escherichia coli
|
6.44
%
|
|
|
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600)
|
Klebsiella pneumoniae
|
14.17
%
|
|
|
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600)
|
Pseudomonas aeruginosa
|
9.79
%
|
|
|
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600
|
Acinetobacter baumannii
|
34.02
%
|
|
|
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630
|
Candida albicans
|
1.69
%
|
|
|
Antifungal activity against Cryptococcus neoformans H99 ATCC 208821 (CO-ADD:FG_002); MIC in YNB media using NBS plates, by Resazurin OD(600-570)
|
Cryptococcus neoformans
|
1.85
%
|
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging
|
Homo sapiens
|
-4.99
%
|
|
Title : Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
Year : 2020
Authors : Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek
Abstract : To identify possible candidates for progression towards clinical studies against SARS-CoV-2, we screened a well-defined collection of 5632 compounds including 3488 compounds which have undergone clinical investigations (marketed drugs, phases 1 -3, and withdrawn) across 600 indications. Compounds were screened for their inhibition of viral induced cytotoxicity using the human epithelial colorectal adenocarcinoma cell line Caco-2 and a SARS-CoV-2 isolate. The primary screen of 5632 compounds gave 271 hits. A total of 64 compounds with IC50 <20 µM were identified, including 19 compounds with IC50 < 1 µM. Of this confirmed hit population, 90% have not yet been previously reported as active against SARS-CoV-2 in-vitro cell assays. Some 37 of the actives are launched drugs, 19 are in phases 1-3 and 10 pre-clinical. Several inhibitors were associated with modulation of host pathways including kinase signaling P53 activation, ubiquitin pathways and PDE activity modulation, with long chain acyl transferases were effective viral inhibitors.
|
Binding affinity to MET in CD-1 mouse cochlear outer hair cells measured at +16 mV membrane potential by patch clamp assay
|
Mus musculus
|
100.0
nM
|
|
Journal : J Med Chem
Title : Design, Synthesis, and Biological Evaluation of a New Series of Carvedilol Derivatives That Protect Sensory Hair Cells from Aminoglycoside-Induced Damage by Blocking the Mechanoelectrical Transducer Channel.
Year : 2019
Volume : 62
Issue : 11
First Page : 5312
Last Page : 5329
Authors : O'Reilly M, Kirkwood NK, Kenyon EJ, Huckvale R, Cantillon DM, Waddell SJ, Ward SE, Richardson GP, Kros CJ, Derudas M.
Abstract : Aminoglycosides (AGs) are broad-spectrum antibiotics used for the treatment of serious bacterial infections but have use-limiting side effects including irreversible hearing loss. Here, we assessed the otoprotective profile of carvedilol in mouse cochlear cultures and in vivo zebrafish assays and investigated its mechanism of protection which, we found, may be mediated by a block of the hair cell's mechanoelectrical transducer (MET) channel, the major entry route for the AGs. To understand the full otoprotective potential of carvedilol, a series of 18 analogues were prepared and evaluated for their effect against AG-induced damage as well as their affinity for the MET channel. One derivative was found to confer greater protection than carvedilol itself in cochlear cultures and also to bind more tightly to the MET channel. At higher concentrations, both carvedilol and this derivative were toxic in cochlear cultures but not in zebrafish, suggesting a good therapeutic window under in vivo conditions.
|
Displacement of [3H]DHA from beta2 adrenergic receptor (unknown origin) stably expressed in HEK293 cell membranes measured after 90 mins by scintillation counting analysis
|
Homo sapiens
|
0.195
nM
|
|
Journal : J Med Chem
Title : Probing the Existence of a Metastable Binding Site at the β<sub>2</sub>-Adrenergic Receptor with Homobivalent Bitopic Ligands.
Year : 2019
Volume : 62
Issue : 17
First Page : 7806
Last Page : 7839
Authors : Gaiser BI, Danielsen M, Marcher-Rørsted E, Røpke Jørgensen K, Wróbel TM, Frykman M, Johansson H, Bräuner-Osborne H, Gloriam DE, Mathiesen JM, Sejer Pedersen D.
Abstract : Herein, we report the development of bitopic ligands aimed at targeting the orthosteric binding site (OBS) and a metastable binding site (MBS) within the same receptor unit. Previous molecular dynamics studies on ligand binding to the β<sub>2</sub>-adrenergic receptor (β<sub>2</sub>AR) suggested that ligands pause at transient, less-conserved MBSs. We envisioned that MBSs can be regarded as allosteric binding sites and targeted by homobivalent bitopic ligands linking two identical pharmacophores. Such ligands were designed based on docking of the antagonist (<i>S</i>)-alprenolol into the OBS and an MBS and synthesized. Pharmacological characterization revealed ligands with similar potency and affinity, slightly increased β<sub>2</sub>/β<sub>1</sub>AR-selectivity, and/or substantially slower β<sub>2</sub>AR off-rates compared to (<i>S</i>)-alprenolol. Truncated bitopic ligands suggested the major contribution of the metastable pharmacophore to be a hydrophobic interaction with the β<sub>2</sub>AR, while the linkers alone decreased the potency of the orthosteric fragment. Altogether, the study underlines the potential of targeting MBSs for improving the pharmacological profiles of ligands.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
4.881
%
|
|
Title : Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
Year : 2020
Authors : Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani
Abstract : Compound repurposing is an important strategy being pursued in the identification of effective treatment against the SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (M-Pro), also termed 3CL-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyprotein into 11 non-structural proteins. We report the results of a screening campaign involving ca 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and chemicals regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, but we have also identified 68 compounds with IC50 lower than 1 uM and 127 compounds with IC50 lower than 5 uM. Profiling showed 67% of confirmed hits were selective (> 5 fold) against other Cys- and Ser- proteases (Chymotrypsin and Cathepsin-L) and MERS 3CL-Pro. Selected compounds were also analysed in their binding characteristics.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.34
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.34
%
|
|
Title : Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
Year : 2020
Authors : Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen
Abstract : Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anti-cytopathic IC50 < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.
